What is the recommended anticoagulation therapy for pregnant women?

Anticoagulation Therapy in Pregnant Women

Low-molecular-weight heparin (LMWH) is the anticoagulant of choice for pregnant women requiring anticoagulation therapy, as it does not cross the placenta and has a better safety profile compared to other anticoagulants. 1

General Principles for Anticoagulation in Pregnancy

First-Line Therapy

• LMWH is recommended over unfractionated heparin (UFH) for both prevention and treatment of venous thromboembolism (VTE) during pregnancy (Grade 1B) 2
• For women receiving vitamin K antagonists who become pregnant, LMWH should replace warfarin immediately upon pregnancy confirmation (Grade 1A for first trimester, Grade 1B for second and third trimesters) 2

Contraindicated Medications

• Oral direct thrombin inhibitors (e.g., dabigatran) and factor Xa inhibitors (e.g., rivaroxaban, apixaban) should be avoided during pregnancy (Grade 1C) 2, 1
• Fondaparinux should be limited to pregnant women with severe allergic reactions to heparin who cannot receive danaparoid (Grade 2C) 2, 1
• Vitamin K antagonists (warfarin) should be avoided due to risk of embryopathy in the first trimester and fetal/neonatal hemorrhage in the third trimester 1

LMWH Dosing Regimens

Treatment of Acute VTE

• Weight-adjusted therapeutic dosing:
  • Enoxaparin: 1 mg/kg twice daily or 1.5 mg/kg once daily
  • Dalteparin: 100 units/kg twice daily or 200 units/kg once daily
  • Tinzaparin: 175 units/kg once daily 2, 1
• Either once-daily or twice-daily dosing regimens are acceptable (conditional recommendation) 2

Prophylactic Dosing

• Standard prophylactic dose:
  • Enoxaparin 40 mg once daily
  • Dalteparin 5,000 units once daily
  • Tinzaparin 4,500 units once daily 2
• For women at higher risk, intermediate-dose LMWH may be used:
  • Enoxaparin 40 mg twice daily
  • Dalteparin 5,000 units twice daily 2

Monitoring and Dose Adjustment

• Routine monitoring of anti-Xa levels is not recommended for most pregnant women receiving LMWH (conditional recommendation) 2, 3
• Anti-Xa monitoring should be considered in specific situations:
  • Women with mechanical heart valves
  • Women at extremes of body weight (<50 kg or >100 kg)
  • Renal impairment
  • Recurrent thrombosis despite anticoagulation 1, 4
• Dose adjustments are common during pregnancy, particularly for prophylactic dosing where requirements may increase significantly as pregnancy progresses 4, 5

Special Clinical Scenarios

Mechanical Heart Valves

For pregnant women with mechanical heart valves, one of the following anticoagulant regimens is recommended (Grade 1A) 2:

1. Adjusted-dose twice-daily LMWH throughout pregnancy with anti-Xa monitoring
2. Adjusted-dose UFH throughout pregnancy with aPTT monitoring
3. UFH or LMWH until week 13, then vitamin K antagonists until close to delivery, then return to UFH/LMWH

For women at very high risk of thromboembolism with mechanical valves, consider adding low-dose aspirin (75-100 mg/day) 2

Peripartum Management

• For women receiving therapeutic LMWH, scheduled delivery with prior discontinuation of anticoagulation is suggested 2
• Discontinue LMWH 24 hours before planned delivery 1
• Resume anticoagulation 12-24 hours after delivery if no bleeding complications 1
• If epidural analgesia is desired, LMWH must be discontinued at least 24 hours prior to insertion of epidural needle 1

Breastfeeding

• UFH, LMWH, warfarin, acenocoumarol, fondaparinux, and danaparoid are all safe options during breastfeeding (strong recommendation) 2

Common Pitfalls and Caveats

1. Inadequate dosing: Standard fixed doses of LMWH that work in non-pregnant patients may be inadequate during pregnancy due to physiological changes. Weight-based dosing is preferred, and dose requirements may increase as pregnancy progresses 4, 5

2. Mechanical heart valves: Despite therapeutic anti-Xa levels, pregnant women with mechanical heart valves remain at risk for valve thrombosis. Close monitoring and multidisciplinary management are essential 6, 3

3. Epidural/spinal anesthesia: Timing of LMWH discontinuation is critical to avoid spinal hematoma. LMWH should be stopped at least 24 hours before neuraxial anesthesia and not restarted until 4 hours after epidural catheter removal 1

4. Transitioning between anticoagulants: Women on long-term vitamin K antagonists should switch to LMWH immediately upon pregnancy confirmation rather than preemptively when attempting pregnancy (Grade 2C) 2

5. Postpartum management: Anticoagulation should continue for at least 6 weeks postpartum with a minimum total duration of 3 months for treatment of VTE 1